Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Int J Cancer. 2010 Jul 1;127(1):86-92. doi: 10.1002/ijc.25027.
Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori-induced gastric cancer. Interleukin (IL)-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical function in inflammation and probably in cancer. We conducted a case-control study including 1,010 gastric cancer patients and 800 healthy controls to assess the association between IL-17A G197A and IL-17F A7488G polymorphisms and risk of gastric cancer. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Logistic regression and Cox-proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features and survival. After adjusted for age and gender, IL-17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer compared with AA genotype [OR 1.51, 95% confidence interval (CI): 1.22-1.87 for GA; OR 1.61, 95% CI: 1.03-2.51 for GG]. Further stratification analyses indicated that the effect of IL-17F 7488GA genotype was noteworthy in gastric cancer patients of noncardia, intestinal type, poorly and moderately differentiated, age older than 40, large tumor size and lymph node metastasis. IL-17A 197AG genotype was associated with increased risk of poorly differentiated, TNM I/II, age of 40-65-year subtypes of gastric cancer, but not with total gastric cancer risk (p = 0.098). No significant relationship was observed between polymorphisms and survival of gastric cancer patients. These findings suggest that polymorphism of IL-17F 7488 involved in susceptibility to gastric cancer, which also influenced certain subtypes according to clinicopathological features, whereas IL-17A 197 may be less relevant.
慢性炎症是幽门螺杆菌引起胃癌发病机制的标志。白细胞介素（IL）-17A 和 IL-17F 是由新型 CD4+Th 细胞亚群表达的炎症细胞因子，在炎症中发挥关键作用，可能在癌症中也发挥作用。我们进行了一项病例对照研究，纳入了 1010 例胃癌患者和 800 例健康对照者，以评估 IL-17A G197A 和 IL-17F A7488G 多态性与胃癌风险之间的关系。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和 DNA 测序来确定基因型。使用逻辑回归和 Cox 比例风险分析来评估多态性与胃癌易感性、临床病理特征和生存之间的关系。在调整年龄和性别后，与 AA 基因型相比，IL-17F 7488GA 和 GG 基因型与胃癌风险增加相关[GA 的比值比（OR）1.51，95%置信区间（CI）：1.22-1.87；GG 的 OR 1.61，95%CI：1.03-2.51]。进一步的分层分析表明，IL-17F 7488GA 基因型在非贲门、肠型、低分化和中分化、年龄大于 40 岁、肿瘤较大和淋巴结转移的胃癌患者中具有显著影响。IL-17A 197AG 基因型与低分化、TNM I/II、年龄在 40-65 岁的胃癌亚型相关，但与总胃癌风险无关（p = 0.098）。多态性与胃癌患者的生存之间未观察到显著关系。这些发现表明，IL-17F 7488 多态性与胃癌易感性有关，并且根据临床病理特征，还影响某些亚型，而 IL-17A 197 可能相关性较小。
